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Abstract Two-dimensional (2D) materials, as adsorbents, have garnered great attention in removing heavy metal ions (HMIs) from drinking water due to their extensive exposed adsorption sites. Nevertheless, there remains a paucity of experimental research to remarkably unlock their adsorption capabilities and fully elucidate their adsorption mechanisms. In this work, exceptional lead ion (Pb2+) (a common HMI) removal capacity (up to 758 mg g−1) is achieved using our synthesized metallic 1T/1T′ phase 2D transition metal dichalcogenide (TMD, including MoS2, WS2, TaS2, and TiS2) nanosheets, which hold tremendous activated S chemisorption sites. The residual Pb2+ concentration can be reduced from 2 mg L−1 to 2 μg L−1 within 0.5 min, meeting the drinking water standards following World Health Organization guideline (Pb2+ concentrations

Highlights Surface energy and surface Pourbaix diagram reveal that ZrO2 ( $$\overline{1 }11$$ 1 ¯ 11 ) is the most thermodynamically stable facet and is preferentially occupied by HO* at the equilibrium potential of oxygen evolution reaction (OER). Microkinetic modeling analyzed the OER activity of 40 single-metal doped ZrO2 and identified 16 metals exhibit improved catalytic activity, with Rh and Fe dopants showing the remarkable improvement. Thermodynamic free energy diagrams, density of states analysis, and ab initio molecular dynamics simulations further confirm that Fe–ZrO2 and Rh–ZrO2 are highly promising catalysts for OER, showcasing low ΔG for the rate-determining step, high conductivity, and exceptional stability.

Background: Even with significant advancements, treating multiple myeloma (MM) remains difficult. At present, the main treatment methods include combined treatment of stem cell transplantation, drug treatment, etc. With the clarification of the molecular biological mechanism of MM, as well as the in-depth study of the internal signal of myeloma cells and the microenvironment of MM patients, more and more new drugs targeting myeloma and microenvironment are gradually used in clinical maintenance treatment, such as inhibit the proteosome: ixazomib, bortezomib and carfilzomib, immune - modulators: thalidomide and lenalidomide, monoclonal antibodies, etc. have made great progress in MM maintenance treatment. With the continuous development of proteasome inhibitor maintenance treatment in MM, the prognosis of the disease has been significantly improved. Our aim is to evaluate the effectiveness and adverse reactions of proteasome inhibitors in maintenance therapy for multiple myeloma, providing new ideas for clinical medication. Methods: Four databases containing randomized controlled studies on the effectiveness and safety of proteasome inhibitors in the maintenance therapy of multiple myeloma are retrieved by the computer. Once the quality of the literature has been thoroughly evaluated, run the data via the RevMan 5.3 software. Results: Eventually 8 studies were added in this systematic review. Compared with the placebo group, proteasome inhibitor in maintenance treatment of multiple myeloma patients with prolonged the survival without progression and overall existence. 5 studies reported the peripheral neuropathy of multiple myeloma in the treatment group compared to placebo group, which was remarkably greater (OR: 1.98; 95 % Cl: 1.35, 2.92; P

Intelligent Product Development of Industry 4.0, systematic and thorough study in Chinese circumstances is uncommon. It is a new idea that requires study progress for precise definitions and measures. This article is conceptual research that aims to analyze and prioritize essential elements for smart product developments as a research model connected to industry 4.0 in the Indian environment. An effective product development framework (EPDF) is proposed in this article that develops a decision-making model based on the consumer and risk assessment model. Technological advances, project management, collaborative development, lean processes and environmentalism are key elements mentioned. For the arrival of the Decision Structure, specific recommendations have been taken. The Technique for Order of Preference by Similarity to Ideal Solution (TOPSIS) technique has been used to understand priority variables considered by individuals and organizations. This paper contributes to stronger 4.0 SPD, followed by agile and sustainable development in the Chinese economy. Regarding its contributions, this research's results can help users make real-time judgments by making optimal use of resources, using highly personalized goods in a shorter lead time. Decision-makers can utilize the suggested decision-making framework, gain a thorough grasp of the conception of current policy in the light of Industry 4.0 and its associated smart products deployment aspects, specifically in the Chinese scenario.

Abstract Background & aim Associating liver partition and portal vein ligation (PVL) for staged hepatectomy (ALPPS) is a creative strategy for enlarging the future liver remnant (FLR) and increasing the tumor resectability rate. However, the indications for ALPPS must have a certain limit when the FLR is too small. We aimed to establish a modified ALPPS model with more widen applicability in rats. Methods An extreme ALPPS model was established in rodents with only a 6.5% FLR. The portal vein (PV) was subjected to restriction to different degrees, then the portal vein pressure (PVP) was measured. Then, different modifications of ALPPS, including hepatic artery restriction (HAR), gradual portal vein restriction (GPVR), and GPVR-associated HAR (HAR+GPVR), were applied in the extreme ALPPS models. Results PVL or PVR provoked an immediate increase in the PVP. The PVP in the PVR -1.28 mm, PVR -0.81 mm, PVR -0.63 mm, and PVL groups was 11.05±1.57 cmH2O, 16.18±1.92 cmH2O, 20.66±1.99 cmH2O, and 24.10±3.33 cmH2O, respectively, and the corresponding 3-day survival rate was 100%, 90.09%, 36.33% and 0, respectively. Then, in the extreme ALPPS model, the growth ratio of the FLR in the control, HAR, GPVR, and HAR+GPVR groups was 0.43±0.21, 0.50±0.16, 4.80±0.86, and 7.40±2.56, and as a consequence, the corresponding 30-day survival rate was 9.09%, 15.38%, 84.61% and 92.90%, respectively. Conclusion ALPPS itself has a limit, and high PVP after PVL contributes to postoperative death in the extreme ALPPS model. Furthermore, a modified method for extreme ALPPS is proposed, i.e., GPVR+HAR in place of PVL, which significantly improves the survival rate of extreme hepatectomy in rat models.

Aims To validate the hypothesis that hepatic vein ligation (HVL) alone may produce similar results to liver venous deprivation (LVD or HVL + portal vein ligation [PVL]). Methods Rats were assigned to five groups, namely, the control group; the R group in which the right median hepatic vein (RMHV) was ligated; the M group in which the middle median hepatic vein (MMHV) was ligated; the RM group in which both the RMHV and MMHV were ligated (R + MMHVL, extended ligation of the hepatic veins); and the LVD group in which both the right median portal vein and the RMHV were ligated. The liver hypertrophy effect and liver enzymes were determined. Methylene blue staining and retrograde pressurized perfusion assays were performed to investigate the hemodynamic changes. Results The RM and LVD groups exhibited similar significant hypertrophy in the future liver remnants when compared to that of the control group, and almost no additional hypertrophy effect was observed in the R and M groups. There was a remarkable elevation in serum transaminase levels in both groups. The methylene blue staining experiment indicated that pressure-dependent collaterals formed between the contiguous drainage areas, and the R + MMHVL procedure blocked the outflow of the right median lobe. Conclusion Extended ligation of the hepatic vein (R + MMHVL) resulted in a similar hypertrophy effect and hepatic damage to those of LVD (HVL + PVL) treatment in a rat model, and intrahepatic venovenous collaterals play key roles.

Nicosulfuron, an acetolactate synthase (ALS) inhibitor herbicide, is a broad-spectrum and highly effective post-emergence herbicide. Glycosyltransferases (GTs) are widely found in organisms and transfer sugar molecules from donors to acceptors to form glycosides or sugar esters, thereby altering the physicochemical properties of the acceptor molecule, such as participating in detoxification. In this study, nine glycosyltransferases in group D of the apple glycosyltransferase family I were predicted to possibly be involved in the detoxification metabolism of ALS-inhibiting herbicides based on gene chip data published online. In order to confirm this, we analysed whether the expression of the nine glycosyltransferase genes in group D was induced by the previously reported ALS-inhibiting herbicides by real-time PCR (polymerase chain reaction). It was found that the ALS-inhibiting herbicide nicosulfuron significantly increased the expression of the MdUGT73CG22 gene in group D. Further investigation of the mechanism of action revealed that the apple glycosyltransferase MdUGT73CG22 glycosylated and modified nicosulfuron both in vivo and ex vivo to form nicosulfuron glycosides, which were involved in detoxification metabolism. In conclusion, a new glycosyltransferase, MdUGT73CG22, was identified for the first time in this study, which can glycosylate modifications of the ALS-inhibiting herbicide nicosulfuron and may be involved in the detoxification process in plants, which can help to further improve the knowledge of the non-targeted mechanism of herbicides.

Grapevine is one of the most economically important fruit crops cultivated worldwide. However, grapevine is highly susceptible to virus infections and exposed to the most diverse forms of viral diseases compared to other fruit crops, and virus-induced incompatibility affects plant growth to different degrees ranging from decline to death. The influence of virus-induced incompatibility could be mitigated to an acceptable level by using appropriate rootstocks. However, the viral tolerance of various grapevine rootstocks with diverse genetic backgrounds remains unclear, along with the identification of the specific viral tolerance factors. In this study, the viral tolerance of 21 grapevine rootstocks was evaluated in a green grafting system. Cabernet Franc varieties infected with a single virus [grapevine leafroll associated virus-1 (GLRaV-1)], a co-infection of two viruses (GLRaV-1 plus grapevine virus A—GVA), and no infection were used as the scions, respectively. The vegetative growth and photosynthetic function of the grafts were analyzed 4 months after grafting. The results indicated that some rootstocks could alleviate the influence of the virus infection, with vegetative growth and photosynthetic function sustained at a normal level, whereas other rootstocks were susceptible to the virus infection, resulting in a decline in the growth and photosynthetic function of the grafts. Our research provides evidence for the existence and diversity of viral tolerance among grapevine rootstocks, offering important information for appropriate rootstock selection in the establishment of new vineyards and in the breeding of grapevine rootstocks with enhanced viral tolerance.

Background Multiple myeloma (MM) is a rare haematological disorder with few therapeutic options. BIBR1532, a telomerase inhibitor, is widely used in cancer treatment and has promising outcomes. In this study, we investigated the efficacy and mechanism of action of BIBR1532 in MM. Methods K562 and MEG-01 cells were cultured with BIBR1532 at different concentrations. After 24 and 48 h, cell survival was analyzed. Next, these cells were cultured with 25 and 50 µM BIBR1532 for 48 h, then, cell proliferation, apoptosis, and the expression of the telomerase activity related markers were tested by 5-Ethynyl-2′-deoxyuridine (EdU) staining, flow cytometric analysis, western blot and quantitative real-time PCR (qRT-PCR), respectively. Expression of Bcl-xL, Bad, Survivin, phosphorylation of PI3K, AKT, mTOR, ERK1/2, and MAPK were tested via western blotting. Further experiments were conducted to evaluate the synergistic effects of BIBR1532 and doxorubicin (Dox) or bortezomib (Bor). Results BIBR1532 inhibited K562 and MEG-01 cell survival in a dose- and time-dependent manner. In addition, BIBR1532 hindered cell proliferation while promoting apoptosis, and this effect was enhanced by increasing the BIBR1532 concentration. Moreover, BIBR1532 inhibited TERT and c-MYC expression, PI3K, AKT, mTOR phosphorylation, and facilitated ERK1/2 and MAPK phosphorylation. Additionally, BIBR1532 combined with Dox or Bor showed synergistic effects in MM treatment. Conclusion BIBR1532 inhibits proliferation and promotes apoptosis in MM cells by inhibiting telomerase activity. Additionally, BIBR1532 combined with Dox or Bor exhibited synergistic effects, indicating that BIBR1532 may be a novel medicine for the treatment of MM.

The design and synthesis of efficient adsorbents for the recovery of precious metals from secondary resources are of great environmental and economic significance. Herein, a magnetic sulfur‐doped composite CoFe2O4@S–CoWO4 (CF@S–CoWO4) is developed through a hydrothermal synthesis method, which is used to selectively recover gold in aqueous media. Significantly, CF@S–CoWO4 exhibits the best overall performance with gold ions adsorption capacity (Qmax) and distribution coefficient (Kd) are 1049 mg g−1 and 4.4 × 106 mL g−1, respectively, which are much higher than those of other gold adsorption materials. The selectivity coefficients (K) toward other metal ions (Pd2+, Ca2+, Mg2+, Cd2+, Al3+, Li+, Ni+) are also higher, which suggests that CF@S–CoWO4 had a preferential selectivity for Au3+ in coexisting ion solutions. Moreover, the antianion interference of the composite follows the order: SO42− > PO43− > NO3− > CO32−, and it also shows very good reusability with adsorption efficiency at 81.78% after four repeated cycles. Based on characterizations and calculation, it is found that Au(III) mainly undergoes chelation and reduction reactions in the S sites in CF@S–CoWO4, which indicates the important role of S sites. Hence the CF@S–CoWO4 composite demonstrates a promising application for the recycling of gold ions from electronic wastewater.

Abstract. Background:. The study aimed to clarify the characteristics of lymph node metastasis (LNM) and to compare the oncologic outcomes of minimally invasive esophagectomy (MIE) with open esophagectomy (OE) in terms of lymph node dissection (LND) in thoracic esophageal cancer patients. Methods:. The data from esophageal cancer patients who underwent MIE or OE from January 2016 to January 2019 were retrospectively reviewed. The characteristics of LNM in thoracic esophageal cancer were discussed, and the differences in numbers of LND, LND rate, and LNM rate/degree of upper mediastinum between MIE and OE were compared. Results:. For overall characteristics of LNM in 249 included patients, the highest rate of LNM was found in upper mediastinum, while LNM rate in middle and lower mediastinum, and abdomen increased with the tumor site moving down. The patients were divided into MIE (n = 204) and OE groups (n = 45). In terms of number of LND, there were significant differences in upper mediastinum between MIE and OE groups (8 [5, 11] vs. 5 [3, 8], P

BackgroundQing-Kai-Ling (QKL) oral liquid, evolving from a classical Chinese formula known as An-Gong-Niu-Huang pills, is a well-established treatment for pneumonia with its mechanism remaining muddled. Studies have shown that the regulation of both intestinal flora and host-microbiota co-metabolism may contribute to preventing and treating pneumonia. The study aimed to investigate the potential mechanism by which QKL alleviates pneumonia from the perspective of ‘microbiota-metabolites-host’ interaction.MethodsWe evaluated the therapeutic effects of QKL on lipopolysaccharide (LPS)-induced pneumonia rats. To explore the protective mechanism of QKL treatment, a multi-omics analysis that included 16S rDNA sequencing for disclosing the key intestinal flora, the fecal metabolome to discover the differential metabolites, and whole transcriptome sequencing of lung tissue to obtain the differentially expressed genes was carried out. Then, a Spearman correlation was employed to investigate the association between the intestinal flora, the fecal metabolome and inflammation-related indices.ResultsThe study demonstrated that pneumonia symptoms were significantly attenuated in QKL-treated rats, including decreased TNF-α, NO levels and increased SOD level. Furthermore, QKL was effective in alleviating pneumonia and provided protection equivalent to that of the positive drug dexamethasone. Compared with the Model group, QKL treatment significantly increased the richness and αlpha diversity of intestinal flora, and restored multiple intestinal genera (e.g., Bifidobacterium, Ruminococcus_torques_group, Dorea, Mucispirillum, and Staphylococcus) that were correlated with inflammation-related indices. Interestingly, the intestinal flora demonstrated a strong correlation with several metabolites impacted by QKL. Furthermore, metabolome and transcriptome analyses showed that enrichment of several host-microbiota co-metabolites [arachidonic acid, 8,11,14-eicosatrienoic acid, LysoPC (20:0/0:0), LysoPA (18:0e/0:0), cholic acid, 7-ketodeoxycholic acid and 12-ketodeoxycholic acid] levels and varying lung gene (Pla2g2a, Pla2g5, Alox12e, Cyp4a8, Ccl19, and Ccl21) expression were observed in the QKL group. Moreover, these metabolites and genes were involved in arachidonic acid metabolism and inflammation-related pathways.ConclusionOur findings indicated that QKL could potentially modulate intestinal flora dysbiosis, improve host-microbiota co-metabolism dysregulation and regulate gene expression in the lungs, thereby mitigating LPS-induced pneumonia in rats. The study may provide new ideas for the clinical application and further development of QKL.

BackgroundLupus nephritis (LN) is the most common and severe clinical manifestation of systemic lupus erythematosus (SLE) with considerable morbidity/mortality and limited treatment options. Since kidney biopsy is a relative hysteretic indicator, it is indispensable to investigate potential biomarkers for early diagnosis and predicting clinical outcomes of LN patients. Extracellular proteins may become the promising biomarkers by the secretion into body fluid. Our study linked extracellular proteins with lupus nephritis to identify the emerging biomarkers.MethodsThe expression profiling data were acquired from the Gene Expression Omnibus (GEO) database. Meanwhile, the two gene lists encoding extracellular proteins were collected from the Human Protein Atlas (HPA) and UniProt database. Subsequently, the extracellular protein-differentially expressed genes (EP-DEGs) were screened out, and the key EP-DEGs were determined by MCODE, MCC, and Degree methods via the protein–protein interaction (PPI) network. The expression level, immune characteristics, and diagnostic value of these candidate biomarkers were investigated. Finally, the Nephroseq V5 tool was applied to evaluate the clinical significance of the key EP-DEGs.ResultsA total of 164 DEGs were acquired by comparing LN samples with healthy controls based on GSE32591 datasets. Then, 38 EP-DEGs were screened out through the intersection between DEGs and extracellular protein gene lists. Function enrichment analysis indicated that these EP-DEGs might participate in immune response and constitute the extracellular matrix. Four key EP-DEGs (LUM, TGFBI, COL1A2, and POSTN) were eventually identified as candidate biomarkers, and they were all overexpressed in LN samples. Except that LUM expression was negatively correlated with most of the immune regulatory genes, there was a positive correlation between the remaining three biomarkers and the immune regulatory genes. In addition, these biomarkers had high diagnostic value, especially the AUC value of the LUM–TGFBI combination which reached almost 1 (AUC = 0.973), demonstrating high accuracy in distinguishing LN from controls. Finally, we found a meaningful correlation of these biomarkers with sex, WHO class, and renal function such as glomerular filtration rate (GFR), serum creatinine level, and proteinuria.ConclusionIn summary, our study comprehensively identified four key EP-DEGs exerting a vital role in LN diagnosis and pathogenesis and serving as promising therapeutic targets.

This study investigates whether minimally invasive esophagectomy (MIE) is a safe and effective way for patients with resectable esophageal cancer by comparing the short-term quality of life (QOL) after minimally invasive esophagectomy and open esophagectomy (OE). A total number of 104 patients who underwent esophagectomy from January 2013 to March 2014 were enrolled in this study. These patients were divided into two groups (MIE and OE group). Three scoring scales of quality of life were used to evaluate QOL before the operation and at the first, third, sixth and twelfth months after MIE or OE, which consist of Karnofshy performance scale (KPS), the European Organization for Research and Treatment questionnaire QLQC-30 (EORTC QLQC-30) and esophageal cancer supplement scale (OES-18). The MIE group was higher than the OE group in one-year survival rate (92.54% vs. 72.00%). Significant differences between the two groups were observed in intraoperative bleeding volume (158.53 ± 91.07 mL vs. 228.97 ± 109.33 mL, p = 0.001), and the incidence of postoperative pneumonia (33.33% vs. 58.62%, p = 0.018). The KPS of MIE group was significantly higher than the OE group at the first (80 vs. 70, p = 0.004 < 0.05), third (90 vs. 80, p = 0.006 < 0.05), sixth (90 vs. 80, p = 0.007 < 0.05) and twelfth months (90 vs. 80, p = 0.004 < 0.05) after surgery. The QLQC-30 score of MIE group was better than OE group at first and twelfth months after the operation. The OES-18 score of MIE group was significantly better than OE group at first, sixth and twelfth months after surgery. The short-term quality of life in MIE group was better than OE group.

BackgroundIgA nephropathy (IgAN), the most common type of glomerulonephritis worldwide, can only be diagnosed mainly by renal biopsy owing to lack of effective biomarkers. It is urgent to explore and identify the potential diagnostic biomarkers through assessing the gene expression profiles of patients with IgAN.MethodsTwo datasets were obtained from the Gene Expression Omnibus (GEO) database, including GSE115857 (55 IgAN, 7 living healthy donors) and GSE35487 (25 IgAN, 6 living healthy donors), then underwent differentially expressed genes (DEGs) and function enrichment analyses utilizing R packages. The common gene list was screened out between DEGs and immune-associated genes by Venn diagram, then performed gene-gene interaction, protein-protein interaction (PPI) and function enrichment analyses. Top three immune-associated hub genes were selected by Maximal Clique Centrality (MCC) method, then the expression and diagnostic value of these hub genes were determined. Consensus clustering algorithm was applied to conduct the unsupervised cluster analysis of the immune-associated hub gene list in IgAN. Finally, the Nephroseq V5 tool was applied to identify the expression level of CCL2, FOS, JUN in kidney diseases, as well as the correlation between CCL2, FOS, JUN expression and renal function in the patients with IgAN.ResultsA total of 129 DEGs were obtained through comparing IgAN with healthy controls via the GSE115857 and GSE35487 datasets. Then, we screened out 24 immune-associated IgAN DEGs. CCL2, JUN, and FOS were identified as the top three hub genes, and they were all remarkably downregulated in IgAN. More importantly, CCL2, JUN, and FOS had a high accuracy [area under the curve (AUC) reached almost 1] in predicting IgAN, which could easily distinguish between IgAN patients and healthy individuals. Three distinct subgroups of IgAN were determined based on 24 immune-associated DEGs, with significant differences in the expression of CCL2, JUN, and FOS genes. Finally, CCL2, FOS, JUN were manifested a meaningful association with proteinuria, glomerular filtration rate (GFR), and serum creatinine level.ConclusionIn summary, our study comprehensively uncovers that CCL2, JUN, and FOS may function as promising biomarkers for diagnosis of IgAN.

Streptococcus suis (S. suis) can decrease its virulence or modify local conditions through biofilm formation, which promotes infection persistence in vivo. Biofilm formation is an important cause of chronic drug-resistant S. suis infection. The aim of this study was to evaluate whether tylosin effectively inhibits S. suis biofilm formation by interacting with O-acetylserine (thiol)-lyase B (CysM), a key enzymatic regulator of cysteine synthesis. Biofilm formation of the mutant (ΔcysM) strain was significantly lower compared to the wild-type ATCC 700794 strain. Tylosin inhibited cysM gene expression, decreased extracellular matrix contents, and reduced cysteine, homocysteine, and S-adenosylmethionine levels, indicating its potential value as an effective inhibitor of S. suis biofilm formation. Furthermore, using biolayer interferometry technology and fourier-transform infrared spectroscopy, we found that tylosin and CysM could be combined directly. Overall, these results provide evidence that tylosin inhibits S. suis biofilm formation by interacting with CysM.

Porcine reproductive and respiratory syndrome (PRRS) is a highly contagious disease caused by the porcine reproductive and respiratory syndrome virus (PRRSV). It is characterized by reproductive disorders in pregnant sows and respiratory symptoms in pigs of all ages. Although antiviral drugs, vaccines, and improved management have played a role in the prevention and control of the PRRS, this disease is still prevalent in pig farms. Hence, the prevention, control, and purification of the PRRS have been the main focus. As we all know, traditional Chinese medicines (TCMs) have played a significant role in the history of ancient medicine. Therefore, exploring effective anti-PRRSV TCMs is an essential way to solve the prevention and treatment of PRRSV. In this study, the active sites of the fifth scavenger receptor cysteine-rich domain of the CD163 receptor was first studied by computer-aided drug design technology. Second, virtual screening of TCMs monomers that may bind to active site was conducted. Third, the crude extracts of TCMs rich in the matching monomer were obtained. Finally, the anti-PRRSV effect of crude extracts of TCMs were verified in vitro. To sum up, it was found that Plantago ovata, Rhus chinensis, and Persicaria orientalis had anti-PRRSV effects in vitro, which laid a theoretical foundation for the research and development of anti-PRRSV TCMs. In addition, this exploration strategy could provide a research template for the discovery of TCMs for human viral diseases.

Bazhen is a classic prescription used for the prevention of qi and blood deficiency. The present study aimed to investigate the effects of dietary supplementation with modified Bazhen powder (MBP) on sows during lactation. Forty pure-bred Yorkshire sows on day 100 of gestation were randomly fed a standard diet supplemented with 20 g MBP per sow per day (MBP group) or without (control group) during -14 to 7 days relative to parturition. Results showed that the serum levels of interleukin 2 (IL-2), immunoglobulin A (IgA), and IgG were higher, whereas IL-10 level was lower in sows fed with MBP diet than in controls on day 7 postpartum. A significantly elevated proportion of serum CD4+ T cells and a slight increase in the ratio of CD4+ to CD8+ T cells in the MBP group were also observed. Furthermore, MBP supplementation improved gastrointestinal function of postpartum sows, evidenced by increased levels of motilin, gastrin, and nitric oxide. Ultra high-performance liquid chromatography combined with a quadrupole time of flight and tandem mass spectrometer identified a total of 21 absorbed milk components. 16S rRNA gene amplicon sequencing data revealed that the microbiota diversity of the colostrum and transitional milk in the MBP group was increased. At the genus level, relative abundances of Enterococcus and Anaerostipes were significantly lower in the MBP group on day 0 of lactation. Metabolomic analysis showed that 38 metabolites were upregulated, and 41 metabolites were downregulated in the transitional milk; 31 metabolites were upregulated and 8 metabolites were downregulated in the colostrum in response to MBP. Metabolic pathways, protein digestion and absorption, and biosynthesis of amino acids were enriched in the colostrum and transitional milk. Our findings provide new insights into the beneficial effects of MBP, highlighted by the changes to the microbiota and metabolomic profile of breast milk from sows fed with an MBP-supplemented diet. Thus, MBP should be considered as a potential dietary supplement for lactating sows in pork production.

Stress diarrhea is a major challenge for weaned piglets and restricts pig production efficiency and incurs massive economic losses. A traditional Chinese medicine prescription (QJC) composed of Astragalus propinquus Schischkin (HQ), Zingiber officinale Roscoe (SJ), and Plantago asiatica L. (CQC) has been developed by our laboratory and shows marked anti-stress diarrhea effect. However, the active compounds, potential targets, and mechanism of this effect remain unclear and warrant further investigation. In our study, we verified the bioactive compounds of QJC and relevant mechanisms underlying the anti-stress diarrhea effect through network pharmacology and in vivo experimental studies. After establishing a successful stress-induced diarrhea model, histomorphology of intestinal mucosa was studied, and Quantitative real-time PCR (RT-qPCR) probe was used for the phosphoinositide 3-kinase (PI3K)–Akt signaling pathway to verify the therapeutic effect of QJC on diarrhea. First, using the network pharmacology approach, we identified 35 active components and 130 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in QJC. From among these, we speculated that quercetin, luteolin, kaempferol, scutellarein, and stigmasterol were the main bioactive compounds and assumed that the anti-diarrhea effect of QJC was related to the PI3K–Akt signaling pathway. The RT-qPCR indicated that QJC and its bioactive components increased the expression levels of PI3K and Akt, inhibited the expression of phosphatase and tensin homolog (PTEN), and activated the PI3K–Akt signaling pathway to relieve stress-induced diarrhea. Furthermore, we found that QJC alleviated the pathological condition of small intestine tissue and improved the integrity of the intestinal barrier. Taken together, our study showed that the traditional Chinese medicine QJC, quercetin, luteolin, kaempferol, scutellarein, and stigmasterol alleviated the pathological condition of small intestine tissue and relieved stress-induced diarrhea by increasing the expression levels of PI3K and Akt and inhibiting the expression levels of PTEN.

Chronic kidney disease (CKD) is an incurable progressive disease with the progressive impairment of kidney function, which can accelerate the progression of cardiovascular disease, increase the risk of infection, and lead to related complications such as anemia and bone disease. CKD is to a great extent preventable and treatable, and it is particularly important to improve the early diagnosis, strengthen the research underlying the mechanism of disease occurrence and development, and innovate new intervention measures. Fibroblast growth factor 21 (FGF21) belongs to one of members of endocrine FGF subfamily with evolutionarily conserved functions and performs a vital role in the regulation of energy balance and adipose metabolism. FGF21 needs to rely on β-Klotho protein to specifically bind to FGF receptor (FGFR), which activates the FGF21 signaling exerting the biological function. FGF21 is deemed as an important regulatory factor extensively modulating many cellular functions under physiologic and pathologic conditions. Although the metabolic effect of FGF21 has been extensively studied, its potential biological role in the kidney has not been generally investigated. In this review, we summarize the biological characteristics, regulation and biological function of FGF21 based on the current studies, and briefly discuss the potential relationship with chronic kidney disease.

Abstract Background Studies have demonstrated that antinuclear antibodies (ANAs) may be correlated with neuromyelitis optica spectrum disorder (NMOSD). However, the conflicting results of studies about the value of ANAs in AQP4 antibody‐positive NMOSD patients need to be further investigated. Material Case data were collected from 143 patients with AQP4 antibody‐positive NMOSD. Patients were divided into two groups based on the ANA test results. The analysis of clinical characteristics, laboratory tests, and MRI examination results were compared between two groups: the NMOSD patients with ANA (+) and with ANA (−). Results Disease duration of NMOSD is shorter in the ANA (+) patients with EDSS

Bioactive compounds from Traditional Chinese Medicines (TCMs) are gradually becoming an effective alternative in the control of porcine reproductive and respiratory syndrome virus (PRRSV) because most of the commercially available PRRSV vaccines cannot provide full protection against the genetically diverse strains isolated from farms. Besides, the incomplete attenuation procedure involved in the production of modified live vaccines (MLV) may cause them to revert to the more virulence forms. TCMs have shown some promising potentials in bridging this gap. Several investigations have revealed that herbal extracts from TCMs contain molecules with significant antiviral activities against the various stages of the life cycle of PRRSV, and they do this through different mechanisms. They either block PRRSV attachment and entry into cells or inhibits the replication of viral RNA or viral particles assembly and release or act as immunomodulators and pathogenic pathway inhibitors through cytokines regulations. Here, we summarized the various antiviral strategies employed by some TCMs against the different stages of the life cycle of PRRSV under two major classes, including direct-acting antivirals (DAAs) and indirect-acting antivirals (IAAs). We highlighted their mechanisms of action. In conclusion, we recommended that in making plans for the use of TCMs to control PRRSV, the pathway forward must be built on a real understanding of the mechanisms by which bioactive compounds exert their effects. This will provide a template that will guide the focus of collaborative studies among researchers in the areas of bioinformatics, chemistry, and proteomics. Furthermore, available data and procedures to support the efficacy, safety, and quality control levels of TCMs should be well documented without any breach of data integrity and good manufacturing practices.

Abstract Background Repeated nontreponemal serologic test for syphilis titers is recommended to evaluate treatment response. However, it is unknown whether serum rapid plasma reagin (RPR) titer can serve as a surrogate for determining the efficacy of treatment in general paresis (GP) remains unknown. Methods We retrospectively reviewed data from 105 GP patients, who were divided into two groups (62 CSF RPR+ patients and 43 CSF RPR- patients) according to reactive RPR test status in CSF. Clinical assessment included the Mini-Mental State Examination (MMSE) scores, CSF examinations (WBC count, protein concentration and RPR titer), and serum tests (RPR titer and TPPA). Among the 105 GP patients, 13 CSF RPR+ patients and 6 CSF RPR- patients had a 12 months follow-up of CSF, serum measures and MMSE. Results The median serum RPR titer was significantly higher in CSF RPR+ patients than that in CSF RPR- GP patients, 1:8 [IQR 1:4–1:32] vs. 1:4 [IQR 1:4–1:8] (P

Abstract Prospective epidemiological studies have consistently suggested that pancreatic cancer-associated new-onset diabetes mellitus (PC-DM) represents a potential platform for early diagnose of pancreatic cancer (PC). Despite the studies performed, the mechanism behind this phenomenon remains ambiguous. In this study, we explored the effects of two types of exosomes released by murine pancreatic cancer and ductal epithelial cells on murine skeletal muscle cells. The results show that PC-derived exosomes can readily enter C2C12 myotubes, triggering lipidosis and glucose intake inhibition. We also demonstrate that PC-derived exosomes can inhibit insulin and PI3K/Akt signalling, in which insulin-induced FoxO1 nuclear exclusion is preserved and Glut4 trafficking is impaired. Microarray and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses show that exosomal microRNAs (miRNAs) probably play key roles in this process, an assumption that is corroborated by in vitro studies. These results confirm that the insulin resistance (IR) of skeletal muscle cells is governed by PC-derived exosomes through the insulin and PI3K/Akt/FoxO1 signalling pathways, where exosomal miRNAs potentially contribute to this phenomenon. These novel findings pave the way towards a comprehensive understanding of the cancer theories: “metabolic reprogramming” and “metabolic crosstalk”.

Background: The objective of this study was to investigate the fatigue status and related factors in patients with early-stage non-small cell lung cancer (NSCLC) 1-5 years after surgery. Materials and Methods: This cross-sectional study included 254 patients with stage IA or IB NSCLC, who had undergone surgery. They completed several surveys, including the Brief Fatigue Inventory, Karnofsky Performance Scale, Physical Activity Questionnaire, Baseline Dyspnea Index, Hospital Anxiety and Depression Scale. The association between fatigue and functional status was assessed using Chi-square analysis. Spearman rank correlation and multivariate logistic regression analysis were used to assess the correlation between fatigue and various other factors. Results: The overall incidence of postoperative fatigue was 59.8%. Among patients with moderate to severe fatigue, 21.1% had obvious dysfunction, whereas only 9.6% of patients with mild or no fatigue (χ2 = 5.369; P = 0.02) showed obvious dysfunction. Multivariate logistic regression analysis showed that functional status (odds ratio [OR]: 3.57; 95% confidence interval [CI]: 1.17-6.19), concurrent lung disease (OR: 2.34; 95% CI: 1.08-4.99), depression (OR: 6.39; 95% CI: 2.42-17.35), and anxiety (OR: 2.45; 95% CI: 1.13-4.87) were independent risk factors for fatigue, whereas physical activity (OR: 0.27; 95% CI: 0.11-0.73) could prevent fatigue. Conclusion: More than half of the patients with early-stage NSCLC experienced fatigue 1-5 years after surgery, and moderate to severe fatigue was often associated with obvious dysfunction. The strong association of fatigue with anxiety, depression, and lung complications suggests that fatigue and other symptoms constitute a symptom cluster. Therefore, comprehensive treatment methods may achieve better therapeutic results.

Objective. Esophageal carcinoma (EC) is a frequently common malignancy of gastrointestinal cancer in the world. This study aims to screen key genes and pathways in EC and elucidate the mechanism of it. Methods. 5 microarray datasets of EC were downloaded from Gene Expression Omnibus. Differentially expressed genes (DEGs) were screened by bioinformatics analysis. Gene Ontology (GO) enrichment, Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment, and protein-protein interaction (PPI) network construction were performed to obtain the biological roles of DEGs in EC. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to verify the expression level of DEGs in EC. Results. A total of 1955 genes were filtered as DEGs in EC. The upregulated genes were significantly enriched in cell cycle and the downregulated genes significantly enriched in Endocytosis. PPI network displayed CDK4 and CCT3 were hub proteins in the network. The expression level of 8 dysregulated DEGs including CDK4, CCT3, THSD4, SIM2, MYBL2, CENPF, CDCA3, and CDKN3 was validated in EC compared to adjacent nontumor tissues and the results were matched with the microarray analysis. Conclusion. The significantly DEGs including CDK4, CCT3, THSD4, and SIM2 may play key roles in tumorigenesis and development of EC involved in cell cycle and Endocytosis.

Objective: To explore the factors affecting the intraoperative conversion of video-assisted thoracoscopic surgery (VATS) to thoracotomy in patients with lung cancer. Methods: The clinical data of 80 patients with lung cancer in The Fourth Hospital of Hebei Medical University from May 2019 to December 2021 were retrospectively analyzed. The patients who were treated with VATS alone were included into thoracoscopy group (n= 40), and those who were intraoperatively converted from VATS to thoracotomy were included into conversion group (n= 40). The medical record data were collected, the influencing factors of intraoperative conversion from VATS to thoracotomy were analyzed, and the surgical indexes and postoperative complications were compared between the two groups. Results: Multivariate regression model showed that tumor in the upper lobe, central lung cancer, history of pulmonary tuberculosis, pleural adhesion ≥ Grade-4 and maximum tumor diameter ≥ 35 mm were risk factors for patients with lung cancer undergoing conversion from VATS to thoracotomy (p< 0.05). In the conversion group, the surgical duration and hospital stay were longer, the intraoperative bleeding volume and thoracic drainage volume were larger, and the total incidence of postoperative complications was higher than those in the thoracoscopy group (p< 0.05). Conclusion: Conversion from VATS to thoracotomy may increase the risk of complications in patients with lung cancer. Tumor in the upper lobe, central lung cancer, history of pulmonary tuberculosis, high degree of pleural adhesion and large tumor diameter are risk factors for conversion from VATS to thoracotomy. [ABSTRACT FROM AUTHOR]